Localized infusions of the partial alpha 7 nicotinic receptor agonist SSR180711 evoke rapid and transient increases in prefrontal glutamate release
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
The ability of local infusions of the alpha 7 nicotinic acetycholine receptor (α7 nAChR) partial agonist SSR180711 to evoke glutamate release in prefrontal cortex was determined in awake rats using a microelectrode array. Infusions of SSR180711 produced dose-dependent increases in glutamate levels. The lower dose (1.0μg in 0.4μL) evoked a rapid rise (∼1.0s) in glutamate (1.41±0.30μM above baseline). The higher dose (5.0μg) produced a similarly rapid, yet larger increase (3.51±0.36μM above baseline). After each dose, the glutamate signal was cleared to basal levels within 7-18s. SSR180711-evoked glutamate was mediated by the α7 nAChR as co-infusion of the selective α7 nAChR antagonist α-bungarotoxin (10.0μM)+SSR1808711 (5.0μg) reduced the effect of 5.0μg alone by 87% (2.62 vs. 0.35μM). Finally, the clearance of the SSR180711 (5.0μg)-evoked glutamate was bidirectionally affected by drugs that inhibited (threo-beta-benzyl-oxy-aspartate (TβOA), 100.0μM) or facilitated (ceftriaxalone, 200mg/kg, i.p.) excitatory amino acid transporters. TβOA slowed both the clearance (s) and rate of clearance (μM/s) by 10-fold, particularly at the mid-late stages of the return to baseline. Ceftriaxone reduced the magnitude of the SSR180711-evoked increase by 65%. These results demonstrate that pharmacological stimulation of α7 nAChRs within the prefrontal cortex is sufficient to evoke rapid yet transient increases in glutamate levels. Such increases may underlie the cognition-enhancing effects of the drug in animals; further justifying studies on the use of α7 nAChR-positive modulators in treating cognition-impairing disorders in humans.
Originalsprog | Engelsk |
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Tidsskrift | Neuroscience |
Vol/bind | 255 |
Sider (fra-til) | 55-67 |
ISSN | 0306-4522 |
DOI | |
Status | Udgivet - 2013 |
Eksternt udgivet | Ja |
ID: 204115397